Mutations Associated With High-Grade irAEs in NSCLC Patients Receiving Immunotherapies.

OBJECTIVES: Compared to low-grade irAEs, high-grade irAEs are more often dose-limiting and can alter the long-term treatment options for a patient. Predicting the incidence of high-grade irAEs would help with treatment selection and therapeutic drug monitoring. MATERIALS AND METHODS: We performed a retrospective study of 430 stage III and IV patients with non-small cell lung cancer (NSCLC) who received an immune checkpoint inhibitor (ICI), either with or without chemotherapy, at a single comprehensive cancer center from 2015 to 2022. The study team retrieved sequencing data and complete clinical information, including detailed irAEs medical records. Fisher's exact test was used to determine the association between mutations and the presence or absence of high-grade irAEs. Patients were analyzed separately based on tumor subtypes and sequencing platforms. RESULTS: High-grade and low-grade irAEs occurred in 15.2% and 46.2% of patients, respectively. Respiratory and gastrointestinal irAEs were the 2 most common irAEs. The distribution of patients with or without irAEs was similar between ICI and ICI+chemotherapy-treated patients. By analyzing the mutation data, we identified 5 genes (MYC, TEK, FANCA, FAM123B, and MET) with mutations that were correlated with an increased risk of high-grade irAEs. For the adenocarcinoma subtype, mutations in TEK, MYC, FGF19, RET, and MET were associated with high-grade irAEs; while for the squamous subtype, ERBB2 mutations were associated with high-grade irAEs. CONCLUSION: This study is the first to demonstrate that specific tumor mutations correlate with the incidence of high-grade irAEs in patients with NSCLC treated with an ICI, providing molecular guidance for treatment selection and drug monitoring.

Bacillus coagulans and Clostridium butyricum synergistically alleviate depression in a chronic unpredictable mild stress mouse model through altering gut microbiota and prefrontal cortex gene expression.

Introduction: The prevalence of major depressive disorder (MDD) has gradually increased and has attracted widespread attention. The aim of this study was to investigate the effect of a probiotic compound consisting of Bacillus coagulans and Clostridium butyricum, on a mouse depression model. Methods: Mice were subjected to chronic unpredictable mild stress (CUMS) and then treated with the probiotics at different concentrations. And mice received behavior test such as forced swimming test and tail suspension test. After that, all mice were sacrificed and the samples were collected for analysis. Moreover, prefrontal cortex (PFC) gene expression and the gut microbiota among different groups were also analyzed. Results: Probiotics improved depressive-like behavior in CUMS mice, as indicated by decreased immobility time (p < 0.05) in the forced swimming test and tail suspension test. probiotics intervention also increased the level of 5-hydroxytryptamine (5-HT) in the prefrontal cortex and decreased the adrenocorticotropic hormone (ACTH) level in serum. In addition, by comparing the PFC gene expression among different groups, we found that the genes upregulated by probiotics were enriched in the PI3K-Akt signaling pathway in the prefrontal cortex. Moreover, we found that downregulated genes in prefrontal cortex of CUMS group such as Sfrp5 and Angpt2, which were correlated with depression, were reversed by the probiotics. Furthermore, the probiotics altered the structure of the gut microbiota, and reversed the reduction of cob(II)yrinate a,c-diamide biosynthesis I pathway in CUMS group. Several species like Bacteroides caecimuris and Parabacteroides distasoni, whose abundance was significantly decreased in the CUMS group but reversed after the probiotics intervention, showed significantly positive correlation with depression associated genes such as Tbxas1 and Cldn2. Discussion: These findings suggested that CUMS-induced depression-like behavior can be alleviated by the probiotics, possibly through alterations in the PFC gene expression and gut microbiota.

SLIVER: Unveiling large scale gene regulatory networks of single-cell transcriptomic data through causal structure learning and modules aggregation.

Prevalent Gene Regulatory Network (GRN) construction methods rely on generalized correlation analysis. However, in biological systems, regulation is essentially a causal relationship that cannot be adequately captured solely through correlation. Therefore, it is more reasonable to infer GRNs from a causal perspective. Existing causal discovery algorithms typically rely on Directed Acyclic Graphs (DAGs) to model causal relationships, but it often requires traversing the entire network, which result in computational demands skyrocketing as the number of nodes grows and make causal discovery algorithms only suitable for small networks with one or two hundred nodes or fewer. In this study, we propose the SLIVER (cauSaL dIscovery Via dimEnsionality Reduction) algorithm which integrates causal structural equation model and graph decomposition. SLIVER introduces a set of factor nodes, serving as abstractions of different functional modules to integrate the regulatory relationships between genes based on their respective functions or pathways, thus reducing the GRN to the product of two low-dimensional matrices. Subsequently, we employ the structural causal model (SCM) to learn the GRN within the gene node space, enforce the DAG constraint in the low-dimensional space, and guide each factor to aggregate various functions through cosine similarity. We evaluate the performance of the SLIVER algorithm on 12 real single cell transcriptomic datasets, and demonstrate it outperforms other 12 widely used methods both in GRN inference performance and computational resource usage. The analysis of the gene information integrated by factor nodes also demonstrate the biological explanation of factor nodes in GRNs. We apply it to scRNA-seq of Type 2 diabetes mellitus to capture the transcriptional regulatory structural changes of ß cells under high insulin demand.

TFTG: A comprehensive database for human transcription factors and their targets.

Transcription factors (TFs) are major contributors to gene transcription, especially in controlling cell-specific gene expression and disease occurrence and development. Uncovering the relationship between TFs and their target genes is critical to understanding the mechanism of action of TFs. With the development of high-throughput sequencing techniques, a large amount of TF-related data has accumulated, which can be used to identify their target genes. In this study, we developed TFTG (Transcription Factor and Target Genes) database (http://tf.liclab.net/TFTG), which aimed to provide a large number of available human TF-target gene resources by multiple strategies, besides performing a comprehensive functional and epigenetic annotations and regulatory analyses of TFs. We identified extensive available TF-target genes by collecting and processing TF-associated ChIP-seq datasets, perturbation RNA-seq datasets and motifs. We also obtained experimentally confirmed relationships between TF and target genes from available resources. Overall, the target genes of TFs were obtained through integrating the relevant data of various TFs as well as fourteen identification strategies. Meanwhile, TFTG was embedded with user-friendly search, analysis, browsing, downloading and visualization functions. TFTG is designed to be a convenient resource for exploring human TF-target gene regulations, which will be useful for most users in the TF and gene expression regulation research.

Oxidized sodium alginate hydrogel-mouse nerve growth factor sustained release system promotes repair of peripheral nerve injury.

In recent years, mouse nerve growth factor (mNGF) has emerged as an important biological regulator to repair peripheral nerve injury, but its systemic application is restricted by low efficiency and large dosage requirement. These limitations prompted us to search for biomaterials that can be locally loaded. Oxidized sodium alginate hydrogel (OSA) exhibits good biocompatibility and physicochemical properties, and can be loaded with drugs to construct a sustained-release system that can act locally on nerve injury. Here, we constructed a sustained-release system of OSA-mouse nerve growth factor (mNGF), and investigated the loading and release of the drug through Fourier transform infrared spectroscopy and drug release curves. In vitro and in vivo experiments showed that OSA-mNGF significantly promoted the biological activities of RSC-96 cells and facilitated the recovery from sciatic nerve crush injury in rats. This observation may be attributed to the additive effect of OSA on promoting Schwann cell biological activities or its synergistic effect of cross-activating phosphoinositide 3-kinase (PI3K) through extracellular signal regulated kinase (ERK) signaling. Although the specific mechanism of OSA action needs to be explored in the future, the current results provide a valuable preliminary research basis for the clinical application of the OSA-mNGF sustained-release system for nerve repair.

In situ monitoring of toxic effects of algal toxin on cells by a novel microfluidic flow cytometry instrument.

Algal toxins produced by microalgae, such as domoic acid (DA)1, have toxic effects on humans. However, toxicity tests using mice only yield lethal doses of algal toxins without providing insights into the mechanism of action on cells. In this study, a fast segmentation of microfluidic flow cytometry cell images based on the bidirectional background subtraction (BBS)2 method was developed to get the visual evidence of apoptosis in both bright-field and fluorescence images. This approach enables mapping of changes in cell morphology and activity under algal toxins, allowing for fast (within 60 s) and automated biological detection. By combining microfluidics with flow cytometry, the intricate cellular-level reaction process can be observed in micro samples of 293 T cells and mouse spleen cells, offering potential for future in vitro experiments.

SCInter: A comprehensive single-cell transcriptome integration database for human and mouse.

Single-cell RNA sequencing (scRNA-seq), which profiles gene expression at the cellular level, has effectively explored cell heterogeneity and reconstructed developmental trajectories. With the increasing research on diseases and biological processes, scRNA-seq datasets are accumulating rapidly, highlighting the urgent need for collecting and processing these data to support comprehensive and effective annotation and analysis. Here, we have developed a comprehensive Single-Cell transcriptome integration database for human and mouse (SCInter, https://bio.liclab.net/SCInter/index.php), which aims to provide a manually curated database that supports the provision of gene expression profiles across various cell types at the sample level. The current version of SCInter includes 115 integrated datasets and 1016 samples, covering nearly 150 tissues/cell lines. It contains 8016,646 cell markers in 457 identified cell types. SCInter enabled comprehensive analysis of cataloged single-cell data encompassing quality control (QC), clustering, cell markers, multi-method cell type automatic annotation, predicting cell differentiation trajectories and so on. At the same time, SCInter provided a user-friendly interface to query, browse, analyze and visualize each integrated dataset and single cell sample, along with comprehensive QC reports and processing results. It will facilitate the identification of cell type in different cell subpopulations and explore developmental trajectories, enhancing the study of cell heterogeneity in the fields of immunology and oncology.

Encapsulation of CsPb2Br5 in TiO2 Microcrystals to Enhance Environmental Stability.

All-inorganic lead halide perovskite has emerged as an attractive semiconducting material due to its unique optoelectronic properties. However, its poor environmental stability restricts its broad application. Here, a simple method for the fabrication of CsPb2Br5/TiO2 is investigated. The introduction of p-aminobenzoic acid, which has two functional groups, is critical for the capping of amorphous TiO2 on CsPb2Br5. After calcination at 300 °C, amorphous TiO2 crystallizes into the anatase phase. The CsPb2Br5/TiO2 NCs show high long-term stability in water and enhanced stability against ultraviolet radiation and heat treatment, owing to the chemical stability of TiO2. More importantly, photo-electrochemical characterizations indicate that the formation of TiO2 shells can increase the charge separation efficiency. Hence, CsPb2Br5/TiO2 exhibits improved photoelectric activity owing to the electrical conductivity of the TiO2 in water. This study provides a new route for the fabrication of optoelectronic devices and photocatalysts based on perovskite NCs in the aqueous phase. Furthermore, the present results demonstrate that CsPb2Br5/TiO2 NCs has considerable potential to be used as a photoelectric material in optical sensing and monitoring.

A film-linked electrostatic self-assembly microfluidic chip.

This article proposes a film-linked electrostatic self-assembly microfluidic chip for the first time, designed to be ready-to-use. Barrier films are used to isolate the gas/liquid path microchannels and the pre-stored reagents of the chip before use. Through the linkage design between the film materials, the motion of barrier films is linked to the structural changes inside the chip. Under the combined action of the rebound force of the elastic substrate, the electrostatic adsorption force between the substrates, and the reaction force of the elastic film, the elastic substrate and the liquid storage substrate are instantly bonded, and the self-assembly of the chip is completed within 1 s. By using six independently output programmable sequences to perform the sequential quantitative pumping of pre-stored reagents, the transfer and mixing of samples and pre-stored reagents are automatically driven in a confined space, which greatly reduces the contamination risk and loss rate of samples/reagents, and improves the accuracy and reproducibility of test results. In addition, the microfluidic multi-step reaction driven in parallel can avoid liquid reflux, accurately control the amount of reactant transfer, and realize the quantitative detection of samples. Multiple reactions can be performed synchronously without interference, saving the test time. Since each gas path is independently controllable, the chip can be extended to a variety of biochemical reactions and has the potential to detect a variety of substances.

Use of comprehensive genomic profiling for biomarker discovery for the management of non-small cell lung cancer brain metastases.

Background: Clinical biomarkers for brain metastases remain elusive. Increased availability of genomic profiling has brought discovery of these biomarkers to the forefront of research interests. Method: In this single institution retrospective series, 130 patients presenting with brain metastasis secondary to Non-Small Cell Lung Cancer (NSCLC) underwent comprehensive genomic profiling conducted using next generation circulating tumor deoxyribonucleic acid (DNA) (Guardant Health, Redwood City, CA). A total of 77 genetic mutation identified and correlated with nine clinical outcomes using appropriate statistical tests (general linear models, Mantel-Haenzel Chi Square test, and Cox proportional hazard regression models). For each outcome, a genetic signature composite score was created by summing the total genes wherein genes predictive of a clinically unfavorable outcome assigned a positive score, and genes with favorable clinical outcome assigned negative score. Results: Seventy-two genes appeared in at least one gene signature including: 14 genes had only unfavorable associations, 36 genes had only favorable associations, and 22 genes had mixed effects. Statistically significant associated signatures were found for the clinical endpoints of brain metastasis velocity, time to distant brain failure, lowest radiosurgery dose, extent of extracranial metastatic disease, concurrent diagnosis of brain metastasis and NSCLC, number of brain metastases at diagnosis as well as distant brain failure. Some genes were solely associated with multiple favorable or unfavorable outcomes. Conclusion: Genetic signatures were derived that showed strong associations with different clinical outcomes in NSCLC brain metastases patients. While these data remain to be validated, they may have prognostic and/or therapeutic impact in the future. Statement of translation relevance: Using Liquid biopsy in NSCLC brain metastases patients, the genetic signatures identified in this series are associated with multiple clinical outcomes particularly these ones that lead to early or more numerous metastases. These findings can be reverse-translated in laboratory studies to determine if they are part of the genetic pathway leading to brain metastasis formation.

Cis-Cardio: A comprehensive analysis platform for cardiovascular-relavant cis-regulation in human and mouse.

Cis-regulatory elements are important molecular switches in controlling gene expression and are regarded as determinant hubs in the transcriptional regulatory network. Collection and processing of large-scale cis-regulatory data are urgent to decipher the potential mechanisms of cardiovascular diseases from a cis-regulatory element aspect. Here, we developed a novel web server, Cis-Cardio, which aims to document a large number of available cardiovascular-related cis-regulatory data and to provide analysis for unveiling the comprehensive mechanisms at a cis-regulation level. The current version of Cis-Cardio catalogs a total of 45,382,361 genomic regions from 1,013 human and mouse epigenetic datasets, including ATAC-seq, DNase-seq, Histone ChIP-seq, TF/TcoF ChIP-seq, RNA polymerase ChIP-seq, and Cohesin ChIP-seq. Importantly, Cis-Cardio provides six analysis tools, including region overlap analysis, element upstream/downstream analysis, transcription regulator enrichment analysis, variant interpretation, and protein-protein interaction-based co-regulatory analysis. Additionally, Cis-Cardio provides detailed and abundant (epi-) genetic annotations in cis-regulatory regions, such as super-enhancers, enhancers, transcription factor binding sites (TFBSs), methylation sites, common SNPs, risk SNPs, expression quantitative trait loci (eQTLs), motifs, DNase I hypersensitive sites (DHSs), and 3D chromatin interactions. In summary, Cis-Cardio is a valuable resource for elucidating and analyzing regulatory cues of cardiovascular-specific cis-regulatory elements. The platform is freely available at http://www.licpathway.net/Cis-Cardio/index.html.

Photocatalytic hydrogel film assisted forward osmosis (PFO) for water treatment: Sustainable performance and contaminant control.

The integration of catalytic oxidation with forward osmosis (FO) holds promising potential to address two crucial challenges encountered by FO: fouling and unsustainable performance, but suitable approaches are still rare. Herein, we have successfully developed a photocatalysis-assisted forward osmosis (PFO) system. In the PFO, a self-made porous carbon nitride doped functional carbon nanotube photocatalytic hydrogel film (PCN@CNTM) was engaged in the FO process in an inventive way by simply sticking to the commercial FO membrane surface, preventing damage to the membrane from the catalyst's direct insertion and delaying the assault from the oxidation groups. PFO allowed organic pollutants to decompose in the feed solution (90%) and on the membrane surface, regulating the water chemical potential and giving the FO membrane antifouling properties. This resulted in sustainable water flux (11.8 LMH) with no significant membrane fouling in PFO, whereas in FO alone there was a significant fouling and flux drop (from 12.73 to 7.23 LMH in 4 h). Moreover, the expensive FO membrane was protected while the hydrogel film can be replaced on demand. The PFO exemplifies the concept of synergistic technology integration, presenting a new perspective on harnessing the strengths of distinct technologies in a mutually beneficial manner.

SEanalysis 2.0: a comprehensive super-enhancer regulatory network analysis tool for human and mouse.

Super-enhancers (SEs) play an essential regulatory role in various biological processes and diseases through their specific interaction with transcription factors (TFs). Here, we present the release of SEanalysis 2.0 (http://licpathway.net/SEanalysis), an updated version of the SEanalysis web server for the comprehensive analyses of transcriptional regulatory networks formed by SEs, pathways, TFs, and genes. The current version added mouse SEs and further expanded the scale of human SEs, documenting 1 167 518 human SEs from 1739 samples and 550 226 mouse SEs from 931 samples. The SE-related samples in SEanalysis 2.0 were more than five times that in version 1.0, which significantly improved the ability of original SE-related network analyses ('pathway downstream analysis', 'upstream regulatory analysis' and 'genomic region annotation') for understanding context-specific gene regulation. Furthermore, we designed two novel analysis models, 'TF regulatory analysis' and 'Sample comparative analysis' for supporting more comprehensive analyses of SE regulatory networks driven by TFs. Further, the risk SNPs were annotated to the SE regions to provide potential SE-related disease/trait information. Hence, we believe that SEanalysis 2.0 has significantly expanded the data and analytical capabilities of SEs, which helps researchers in an in-depth understanding of the regulatory mechanisms of SEs.

c-Met Mediated Cytokine Network Promotes Brain Metastasis of Breast Cancer by Remodeling Neutrophil Activities.

The brain is one of the most common metastatic sites among breast cancer patients, especially in those who have Her2-positive or triple-negative tumors. The brain microenvironment has been considered immune privileged, and the exact mechanisms of how immune cells in the brain microenvironment contribute to brain metastasis remain elusive. In this study, we found that neutrophils are recruited and influenced by c-Met high brain metastatic cells in the metastatic sites, and depletion of neutrophils significantly suppressed brain metastasis in animal models. Overexpression of c-Met in tumor cells enhances the secretion of a group of cytokines, including CXCL1/2, G-CSF, and GM-CSF, which play critical roles in neutrophil attraction, granulopoiesis, and homeostasis. Meanwhile, our transcriptomic analysis demonstrated that conditioned media from c-Met high cells significantly induced the secretion of lipocalin 2 (LCN2) from neutrophils, which in turn promotes the self-renewal of cancer stem cells. Our study unveiled the molecular and pathogenic mechanisms of how crosstalk between innate immune cells and tumor cells facilitates tumor progression in the brain, which provides novel therapeutic targets for treating brain metastasis.

Landscape and significance of human super enhancer-driven core transcription regulatory circuitry.

A core transcription regulatory circuitry (CRC) is an interconnected self-regulatory circuitry that is formed by a group of core transcription factors (TFs). These core TFs collectively regulate gene expression by binding not only to their own super enhancers (SEs) but also to the SEs of one another. For most human tissue/cell types, a global view of CRCs and core TFs has not been generated. Here, we identified numerous CRCs using two identification methods and detailed the landscape of the CRCs driven by SEs in large cell/tissue samples. The comprehensive biological analyses, including sequence conservation, CRC activity and genome binding affinity were conducted for common TFs, moderate TFs, and specific TFs, which exhibit different biological features. The local module located from the common CRC network highlighted the essential functions and prognostic performance. The tissue-specific CRC network was highly related to cell identity. Core TFs in tissue-specific CRC networks exhibited disease markers, and had regulatory potential for cancer immunotherapy. Moreover, a user-friendly resource named CRCdb (http://www.licpathway.net/crcdb/index.html) was developed, which contained the detailed information of CRCs and core TFs used in this study, as well as other interesting results, such as the most representative CRC, frequency of TFs, and indegree/outdegree of TFs.

Prognostic Mutational Signatures of NSCLC Patients treated with chemotherapy, immunotherapy and chemoimmunotherapy.

Different types of therapy are currently being used to treat non-small cell lung cancer (NSCLC) depending on the stage of tumor and the presence of potentially druggable mutations. However, few biomarkers are available to guide clinicians in selecting the most effective therapy for all patients with various genetic backgrounds. To examine whether patients' mutation profiles are associated with the response to a specific treatment, we collected comprehensive clinical characteristics and sequencing data from 524 patients with stage III and IV NSCLC treated at Atrium Health Wake Forest Baptist. Overall survival based Cox-proportional hazard regression models were applied to identify mutations that were "beneficial" (HR < 1) or "detrimental" (HR > 1) for patients treated with chemotherapy (chemo), immune checkpoint inhibitor (ICI) and chemo+ICI combination therapy (Chemo+ICI) followed by the generation of mutation composite scores (MCS) for each treatment. We also found that MCS is highly treatment specific that MCS derived from one treatment group failed to predict the response in others. Receiver operating characteristics (ROC) analyses showed a superior predictive power of MCS compared to TMB and PD-L1 status for immune therapy-treated patients. Mutation interaction analysis also identified novel co-occurring and mutually exclusive mutations in each treatment group. Our work highlights how patients' sequencing data facilitates the clinical selection of optimized treatment strategies.

Modulation of oxidative phosphorylation and mitochondrial biogenesis by cigarette smoke influence the response to immune therapy in NSCLC patients.

The treatment regimen of non-small cell lung cancer (NSCLC) has drastically changed owing to the superior anti-cancer effects generated by the immune-checkpoint blockade (ICB). However, only a subset of patients experience benefit after receiving ICBs. Therefore, it is of paramount importance to increase the response rate by elucidating the underlying molecular mechanisms and identifying novel therapeutic targets to enhance the efficacy of IBCs in non-responders. We analyzed the progression-free survival (PFS) and overall survival (OS) of 295 NSCLC patients who received anti-PD-1 therapy by segregating them with multiple clinical factors including sex, age, race, smoking history, BMI, tumor grade and subtype. We also identified key signaling pathways and mutations that are enriched in patients with distinct responses to ICB by gene set enrichment analysis (GSEA) and mutational analyses. We found that former and current smokers have a higher response rate to anti-PD-1 treatment than non-smokers. GSEA results revealed that oxidative phosphorylation (OXPHOS) and mitochondrial related pathways are significantly enriched in both responders and smokers, suggesting a potential role of cellular metabolism in regulating immune response to ICB. We also demonstrated that all-trans retinoic acid (ATRA) which enhances mitochondrial function significantly enhanced the efficacy of anti-PD-1 treatment in vivo. Our clinical and bioinformatics based analyses revealed a connection between smoking induced metabolic switch and the response to immunotherapy, which can be the basis for developing novel combination therapies that are beneficial to never smoked NSCLC patients.

CRdb: a comprehensive resource for deciphering chromatin regulators in human.

Chromatin regulators (CRs) regulate epigenetic patterns on a partial or global scale, playing a critical role in affecting multi-target gene expression. As chromatin immunoprecipitation sequencing (ChIP-seq) data associated with CRs are rapidly accumulating, a comprehensive resource of CRs needs to be built urgently for collecting, integrating, and processing these data, which can provide abundant annotated information on CR upstream and downstream regulatory analyses as well as CR-related analysis functions. This study established an integrative CR resource, named CRdb (http://cr.liclab.net/crdb/), with the aim of curating a large number of available resources for CRs and providing extensive annotations and analyses of CRs to help biological researchers clarify the regulation mechanism and function of CRs. The CRdb database comprised a total of 647 CRs and 2,591 ChIP-seq samples from more than 300 human tissues and cell types. These samples have been manually curated from NCBI GEO/SRA and ENCODE. Importantly, CRdb provided the abundant and detailed genetic annotations in CR-binding regions based on ChIP-seq. Furthermore, CRdb supported various functional annotations and upstream regulatory information on CRs. In particular, it embedded four types of CR regulatory analyses: CR gene set enrichment, CR-binding genomic region annotation, CR-TF co-occupancy analysis, and CR regulatory axis analysis. CRdb is a useful and powerful resource that can help in exploring the potential functions of CRs and their regulatory mechanism in diseases and biological processes.

SEdb 2.0: a comprehensive super-enhancer database of human and mouse.

Super-enhancers (SEs) are cell-specific DNA cis-regulatory elements that can supervise the transcriptional regulation processes of downstream genes. SEdb 2.0 (http://www.licpathway.net/sedb) aims to provide a comprehensive SE resource and annotate their potential roles in gene transcriptions. Compared with SEdb 1.0, we have made the following improvements: (i) Newly added the mouse SEs and expanded the scale of human SEs. SEdb 2.0 contained 1 167 518 SEs from 1739 human H3K27ac chromatin immunoprecipitation sequencing (ChIP-seq) samples and 550 226 SEs from 931 mouse H3K27ac ChIP-seq samples, which was five times that of SEdb 1.0. (ii) Newly added transcription factor binding sites (TFBSs) in SEs identified by TF motifs and TF ChIP-seq data. (iii) Added comprehensive (epi)genetic annotations of SEs, including chromatin accessibility regions, methylation sites, chromatin interaction regions and topologically associating domains (TADs). (iv) Newly embedded and updated search and analysis tools, including 'Search SE by TF-based', 'Differential-Overlapping-SE analysis' and 'SE-based TF-Gene analysis'. (v) Newly provided quality control (QC) metrics for ChIP-seq processing. In summary, SEdb 2.0 is a comprehensive update of SEdb 1.0, which curates more SEs and annotation information than SEdb 1.0. SEdb 2.0 provides a friendly platform for researchers to more comprehensively clarify the important role of SEs in the biological process.

Characteristics of the Gut Microbiota in Young Adults with Autism Spectrum Disorder.

BACKGROUND: Although the characteristics of the gut microbiota of children with autism spectrum disorder (ASD) have been well studied, those of young adults with ASD have seldom been reported. METHODS: Using 16S rRNA gene sequencing, we characterized the gut microbiota of 19 young adults with ASD and compared them with that of 19 healthy adults. A random forest prediction model was used to distinguish between the two groups at the genus level. RESULTS: The abundance levels of one phylum, seven families, and 18 genera in adults with ASD were significantly different from those of controls. The genus Phascolarctobacterium was significantly enriched in adults with ASD, which might elicit ASD-like behavior through production of propionate. In addition, a random forest model identified 15 genera that could distinguish adults with ASD from healthy controls with areas under the receiver operating curve of 92.86%, and ten of them were biomarkers identified by LEfSe. CONCLUSIONS: Our results identified specific gut bacteria associated with ASD, and the successful application of certain genera in the prediction model further supports the association between gut microbiota and ASD.